Enkephalin antinociception in mice is mediated by δ1- and δ2-opioid receptors in the brain and spinal cord, respectively

A. E. Takemori, P. S. Portoghese

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46 Scopus citations


Pharmacological evidence for the existence of δ-opioid receptor subtypes has been reported. This study was conducted to determine which type of δ-opioid receptors was involved supraspinally and spinally when antinociception was induced by the natural enkephalins, [Leu5]enkephalin and [Met5]enkephalin. In the mouse tail flick assay, the antinociceptive ED50 values of both intracerebroventricularly (i.c.v.) administered [Leu5]enkephalin and [Met5]enkephalin (together with the peptidase inhibitors, bestatin and thiorphan) were significantly increased by 7-benzylidenenaltrexone (BNTX), a selective δ1-opioid receptor antagonist but not by naltriben, a selective δ2-opioid receptor antagonist. On the other hand, when the enkephalins were administered intrathecally (i.t.), the antinociceptive ED50 values of both enkephalins were significantly raised by naltriben but not by BNTX. β-Endorphin-induced (i.c.v.) antinociception was antagonized by naltriben administered i.t. or s.c. but not by BNTX administered i.t. or s.c. Different δ-opioid receptor subtypes appeared to be involved in supraspinal (δ1) and spinal (δ2) antinociception induced by endogenous δ-opioid receptor agonists, [Leu5] and [Met5]enkephalin. The antinociception produced by i.c.v. administered β-endorphin has been attributed to the release of [Met5]enkephalin in the spinal cord and its antagonism by naltriben support the finding that enkephalins interact with δ2-opioid receptors in the spinal cord to mediate antinociception. β-Endorphin may be interacting at receptors other than δ1-or δ2-opioid receptors in the brain, perhaps the putative ε receptors, to mediate their effects because neither i.c.v. administered BNTX nor naltriben inhibited its activity.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number2
StatePublished - Sep 28 1993


  • Antinociception
  • BNTX (7-benzylidenenaltrexone)
  • Brain
  • Naltriben
  • Spinal cord
  • [Leu]enkephalin
  • [Met]enkephalin
  • β-Endorphin
  • δ-Opioid receptors
  • δ-Opioid receptors

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